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1.
J Exp Clin Cancer Res ; 39(1): 9, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928530

RESUMO

BACKGROUND: Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS: From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. RESULTS: C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. CONCLUSIONS: Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.

2.
Int J Oncol ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31793655

RESUMO

To evaluate the prognostic and molecular mechanisms of sex and racial differences in gastric cancer, data from two large centers were used to retrospectively analyze the survival of gastric cancer patients with regard to sex and racial differences. In examining the molecular mechanism of sex in gastric cancer patients of different races, data from The Cancer Genome Atlas database were used to analyze differentially expressed genes (DEGs), and Gene Ontology (GO) enrichment and DNA methylation analyses were performed. Among White gastric cancer patients, it was found that the survival prognosis for females was better than that for males; conversely, among Chinese patients, males had a better prognosis. For African Americans, sex may have an impact on gastric cancer, but this relationship was unclear. The core DEGs between the different sexes included glycogenin 2 pseudogene 1, ribosomal protein S4 Y­linked 1, taxilin­Î³ and eukaryotic translation initiation factor 1A X­linked among White patients, and GO enrichment analysis revealed that these genes act mainly through RNA binding and transcription pathways. Among Black patients, core DEGs included DnaJ heat shock protein family (Hsp40) member C5, histone deacetylase 10, neogenin 1 and SMG5 nonsense mediated mRNA decay factor, which are mainly related to pathways of cellular structural changes based on GO enrichment analysis. For Asian patients, core DEGs included zinc finger protein Y­linked, thymosin ß4 Y­linked, zinc finger protein 787 and ubiquitously transcribed tetratricopeptide repeat containing, Y­linked, participating in cell surface receptor­associated signal transduction and G­protein coupled receptor protein signaling pathways, according to GO. The expression of different core genes and differences in pathways are likely to be the main causes affecting the variation observed among gastric cancer patients of different races and sexes.

3.
Future Oncol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799885

RESUMO

Aim: To elucidate the clinicopathological significance and prognostic value of SLC17A9 expression in gastric carcinoma (GC). Methods: SLC17A9 mRNA level and its relationship with TP53 mutation was analyzed. SLC17A9 protein expression was examined by immunohistochemistry in 161 patients. Results: SLC17A9 mRNA and protein expression were higher in GC tissues than in adjacent normal tissues (p < 0.01). SLC17A9 mRNA expression was higher in GC tissues having mutated TP53 than in tissues with wild-type TP53 (p < 0.001). High SLC17A9 expression was also significantly associated with poor overall survival and recurrence-free survival and was also found to be an independent prognostic factor for long-term survival in GC patients.Conclusion: Our results show that SLC17A9 may serve as a potential prognostic biomarker in GC patients.

4.
Biochimie ; 170: 10-20, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31830513

RESUMO

Oxidative stress leads to intestinal epithelial cells damage, which induces tight junction injury and systemic endogenous stress syndrome. The evidence suggests that SIRT1/PGC-1α pathway is closely associated with oxidative damage. However, the mechanism in protecting intestinal epithelial cells against oxidative stress dependant on autopahgy/mitophagy remains to be elucidated. In the current study, we investigated the functional role of SIRT1/PGC-1α pathway on regulation of autopahgy/mitophagy and tight junction protein expression underlying the oxidative dysfunction in porcine intestinal epithelial cells (IPEC-1). Results demonstrated that H2O2 exposure caused high accumulation of ROS, with a decrease of mitochondrial membrane potential and an inhibition of the tight junction molecules in IPEC-1 cells. Also, COX IV mRNA expression and SIRT1/PGC-1α pathway were suppressed. Autophagy and PINK1/Parkin dependant-mitophagy were activated following H2O2 treatment. Further research indicated that activation of SIRT1/PGC-1α pathway caused by specific activator SRT 1720 resulted in elevating autophagy/mitophagy related markers and SIRT1 inhibitor EX 527 reversed these effects. Additionally, SIRT1 activation significantly suppressed the ROS generation, leading to increase mitochondrial membrane potential and COX IV expression. Most importantly, the expression of tight junction molecules contributing to maintain intestinal barrier integrity was significantly up-regulated. Collectively, these findings indicated that autophagy/mitophagy elevation caused by SIRT1/PGC-1α pathway activation might be a protective mechanism to increase tight junction integrity against oxidative stress-mediated ROS production in IPEC-1 cells.

5.
Front Physiol ; 10: 1148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620008

RESUMO

Harmonia axyridis is an important natural predator used in the biological control of insect pests. Vitellogenin (Vg) supplementation to artificial diet can improve fecundity of H. axyridis, however, the effects of Vg on physiology of H. axyridis at the molecular level is unclear. This study investigated the effects of Vg on the physiology (digestive enzyme activities) and transcriptome patterns by feeding H. axyridis adults with treatment (artificial diet with Vg supplement) and control (artificial diet supplemented with bovine serum albumin (BSA). The transcriptome sequencing yielded 43.94 Gb of clean data, and 3,946 differentially expressed genes (DEGs) - including 93 upregulated and 3,853 downregulated genes between the treatment and control. Six DEGs related to development and digestive enzyme were chosen for quantitative real-time PCR (qRT-PCR) to validate the accuracy of the RNA-seq results and confirmed that the transcriptome analysis yielded reliable results. The Vg supplement has increased activities of digestive enzymes and related genes expression in H. axyridis. The transcript level of digestive enzyme genes (apolipoprotein D and phosphoenolpyruvate carboxykinase) were much higher in adults fed on diet supplemented with Vg compared with that of the control.

6.
Eur J Cancer Prev ; 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31567483

RESUMO

The molecular chaperone heat shock protein 90 (Hsp90) is highly expressed in tumor tissue according to many studies. However, there is no large-scale study investigating the expression of Hsp90 in pan-cancer so far, and the molecular mechanisms leading to aberrant Hsp90 expression are also largely unknown. To address these questions, we performed an in silico analysis of Hsp90 expression using mRNA sequencing data from The Cancer Genome Atlas study. The results were further validated using independent datasets. We found that the expression of HSP90AA1, a subtype of Hsp90, was much higher in hepatocellular carcinoma than in adjacent normal liver tissue. A large cancer panel with eight more cancer types revealed a similar trend except for prostate cancer, which had low HSP90AA1 expression in tumor tissue. Heat shock factor 1 followed a similar trend as HSP90AA1, with higher expression in cancer. HSP90AA1 expression was closely related to its copy numbers. Deletion of the HSP90AA1 locus in a subset of hepatocellular carcinoma led to low HSP90AA1 expression. In addition, higher HSP90AA1 expression was associated with poorer prognosis in hepatocellular carcinoma patients. In a multivariable analysis including tumor, node and metastasis stage, HSP90AA1 expression remained a negative prognostic factor, suggesting that the effect of HSP90AA1 was independent of tumor stage. In conclusion, we demonstrated that high HSP90AA1 expression was ubiquitous in cancer and that HSP90AA1 was a potential diagnostic and prognostic biomarker for hepatocellular carcinoma.

7.
Int J Mol Sci ; 20(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505747

RESUMO

Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are the main pathogens for mycoplasmal pneumonia of swine (MPS) and post-weaning multisystemic wasting syndrome (PMWS), respectively. Infection by these pathogens often happens together and causes great economic losses. In this study, a kind of recombinant baculovirus that can display P97R1P46P42 chimeric protein of Mhp and the capsid (Cap) protein of PCV2 was developed, and the protein location was identified. Another recombinant baculovirus was constructed without tag proteins (EGFP, mCherry) and was used to evaluate the immune effect in experiments with BALB/c mice and domestic piglets. Antigen proteins P97R1P46P42 and Cap were expressed successfully; both were anchored on the plasma membrane of cells and the viral envelope. It should be emphasized that in piglet immunization, the recombinant baculovirus vaccine achieved similar immunological effects as the mixed commercial vaccine. Both the piglet and mouse experiments showed that the recombinant baculovirus was able to induce humoral and cellular responses effectively. The results of this study indicate that this recombinant baculovirus is a potential candidate for the further development of more effective combined genetic engineering vaccines against MPS and PMWS. This experiment also provides ideas for vaccine development for other concomitant diseases using the baculovirus expression system.


Assuntos
Vacinas Bacterianas , Circovirus , Engenharia Genética , Mycoplasma hyopneumoniae , Vacinas Virais , Animais , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Circovirus/genética , Circovirus/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Mycoplasma hyopneumoniae/genética , Mycoplasma hyopneumoniae/imunologia , Células Sf9 , Spodoptera , Vacinas Virais/genética , Vacinas Virais/imunologia , Vacinas Virais/farmacologia
8.
Cancer Res ; 79(20): 5159-5166, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31481498

RESUMO

Tumor cells proliferate rapidly and thus are frequently subjected to replication stress and the risk of incomplete duplication of the genome. Fragile sites are replicated late, making them more vulnerable to damage when DNA replication fails to complete. Therefore, genomic alterations at fragile sites are commonly observed in tumors. FRA16D is one of the most common fragile sites in lung cancer, however, the nature of the tumor suppressor genes affected by FRA16D alterations has been controversial. Here, we show that the ATMIN gene, which encodes a cofactor required for activation of ATM kinase by replication stress, is located close to FRA16D and is commonly lost in lung adenocarcinoma. Low ATMIN expression was frequently observed in human lung adenocarcinoma tumors and was associated with reduced patient survival, suggesting that ATMIN functions as a tumor suppressor in lung adenocarcinoma. Heterozygous Atmin deletion significantly increased tumor cell proliferation, tumor burden, and tumor grade in the LSL-KRasG12D; Trp53 F/F (KP) mouse model of lung adenocarcinoma, identifying ATMIN as a haploinsufficient tumor suppressor. ATMIN-deficient KP lung tumor cells showed increased survival in response to replication stress and consequently accumulated DNA damage. Thus, our data identify ATMIN as a key gene affected by genomic deletions at FRA16D in lung adenocarcinoma. SIGNIFICANCE: These findings identify ATMIN as a tumor suppressor in LUAD; fragility at chr16q23 correlates with loss of ATMIN in human LUAD and deletion of Atmin increases tumor burden in a LUAD mouse model.

9.
Bioorg Med Chem ; 27(19): 115015, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31420256

RESUMO

Fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) are mainly expressed in adipocytes and/or macrophages and play essential roles in energy metabolism and inflammation. When FABP4 function is diminished, FABP5 expression is highly increased possibly as a functional compensation. Dual FABP4/5 inhibitors are expected to provide beneficial synergistic effect on treating diabetes, atherosclerosis, and inflammation-related diseases. Starting from our previously reported selective FABP4 inhibitor 8, structural biology information was used to modulate the selectivity profile and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. Two compounds A16 and B8 were identified to show inhibitory activities against both FABP4/5 and good selectivity over FABP3, which could also reduce the level of forskolin-stimulated lipolysis in mature 3T3-L1 adipocytes. Compared with compound 8, these two compounds exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 murine macrophages, with decreased levels of pro-inflammatory cytokines TNFα and MCP-1 and apparently inhibited IKK/NF-κB pathway.

10.
J Anim Physiol Anim Nutr (Berl) ; 103(5): 1521-1529, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328334

RESUMO

Pig transportation is associated with intestinal oxidative stress and results in destruction of intestinal integrity. Autophagy has been contributed to maintain cell homeostasis under stresses. The purpose of this study was to evaluate the effects of transport stress on morphology, intestinal mucosal barrier and autophagy/mitophagy levels in pig jejunum. A total of 16 finishing pigs were randomly divided into two groups. The control group was directly transported to the slaughterhouse and rested for 24 hr. The experimental groups were transported for 5 hr and slaughtered immediately. The results showed that transportation induced obvious stress responses with morphological and histological damage in jejunum accompanying with an elevated level of malondialdehyde (MDA; p < .05), endotoxin (LPS; p < .05), lactic dehydrogenase (LDH; p < .05) and a decreased level of serum superoxide dismutase (SOD; p < .05). Also, hemeoxy genase 1 (HO-1; p < .01) as well as tight junction protein (claudin-1 [p < .001], occludin [p < .05] and zonula occludens 1 [ZO-1; p < 0.05]) levels were attenuated in jejunum tissue, and NADPH oxidase 1 (NOX1; p < .01) mRNA expression was up-regulated. Further research indicated that transport stress could induce autophagy through increasing microtubule-associated protein light chain 3 (LC3; p < .05) and autophagy-related gene 5 (ATG5; p < .01) levels and suppressing p62 expression. Additionally, transport stress increased the protein levels of PTEN-induced putative kinase 1 (PINK1; p < .05) and Parkin (p < .05) which was associated with mitophagy. In conclusions, transport stress could induce the destruction of intestinal integrity and involve in the intestinal mucosal barrier oxidative damage, and also contribute to activation of autophagy/mitophagy.

11.
J Gastrointest Surg ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346960

RESUMO

OBJECTIVES: To evaluate gender differences in initial presentation, pathology and outcomes with GC (GC). METHODS: The 1973-2013 Surveillance Epidemiology and End Results (SEER) 17-registry database was analysed for renal tumours from 1973 to 2013 coded as primary site "stomach". After various exclusions, a final study group of 99,922 cases with complete data was obtained. Demographic variables analysed included age, sex, marital status and race. Tumour variables included size, stage at diagnosis, grade, primary site, treatment and histology. Primary outcome variables included overall survival (OS) and cancer-specific survival (CSS). RESULTS: Overall, 96,501 gastric cancer patients were identified. Of those, 34,862 (36.2%) were women. For woman, log-rank test showed that OS and CSS were significantly longer in man (p < 0.0001). In Cox regression analysis, woman was associated with a significantly improved OS [(HR of death in 1973 to 2003 = 0.87, 95% CI = 0.85-0.89, P < 0.001) (HR of death in 2004 to 2013 = 0.94, 95% CI = 0.91-0.97, P < 0.001)] and cancer-specific survival [(HR of death in 1973 to 2003 = 0.90, 95% CI = 0.87-0.92, P < 0.001) (HR of death in 2004 to 2013 = 0.90, 95% CI = 0.87-0.93, P < 0.001)]. When performing a Kaplan-Meier curve analysis after propensity score matching, gender persisted to be a significant survival of woman for OS and CSS. CONCLUSIONS: Men present with larger, higher stage, higher grade GC than women. OS and CSS are better in women, which is significantly different.

12.
ACS Appl Mater Interfaces ; 11(30): 27394-27401, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31313583

RESUMO

Fluorescence-based detection is one of the most efficient and cost-effective methods for detecting hazardous, aqueous Hg2+. We designed a fluorescent porous organic polymer (TPA-POP-TSC), with a "fluorophore" backbone and a thiosemicarbazide "receptor" for Hg2+-targeted sensing. Nanometer-sized TPA-POP-TSC spheres (nanoPOP) were synthesized under mini-emulsion conditions and showed excellent solution processability and dispersity in aqueous solution. The nanoPOP sensor exhibits exceptional sensitivity (Ksv = 1.01 × 106 M-1) and outstanding selectivity for Hg2+ over other ions with rapid response and full recyclability. Furthermore, the nanoPOP material can be easily coated onto a paper substrate to afford naked eye-based Hg2+-detecting test strips that are convenient, inexpensive, fast, highly sensitive, and reusable. Our design takes advantage of the efficient and selective capture of Hg2+ by thiosemicarbazides (binding energy = -29.84 kJ mol-1), which facilitates electron transfer from fluorophore to bound receptor, quenching the sensor's fluorescence.

13.
Cancer Manag Res ; 11: 4691-4697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191026

RESUMO

Aims: To examine the expression of CXCL16 in colorectal cancer (CRC) tissue and to clarify the relationships between CXCL16 and clinicopathological features and survival in CRC. Methods: A total of 142 consecutive CRC patients undergoing colorectal surgery at the Department of Gastrointestinal Center, First Affiliated Hospital, Sun Yat-sen University, between January 2010 and December 2010 were enrolled in this study. CXCL16 was measured by immunohistochemical staining in CRC tissue. Association between CXCL16 expression and clinicopathologic parameters was analyzed with a chi-square test. Survival curves were calculated by the Kaplan-Meier method, and the differences between CXCL16 high- and low-expression groups were analyzed using the log-rank test. Cox univariate and multivariate analyses were used to determine risk factors for overall survival (OS). Results: CXCL16 expression was elevated in CRC. CXCL16-positive expression was significantly related to tumor size (P=0.043), tumor differentiation (P=0.046) and distant metastasis (P=0.038), and there was a trend toward lymph node metastasis (P=0.070). CXCL16 expression, together with differentiation, depth of invasion, lymph node metastasis, and distant metastasis, was a significant independent prognostic factor for OS of patients with CRC (HR 2.026, 95% CI 1.128-3.640, P=0.018). Conclusion: CXCL16 expression was enhanced in CRC tissue and was negatively correlated with survival in CRC patients. Furthermore, CXCL16-positive expression was an independent prognostic factor for CRC patients, whilst the underlying mechanisms remain unclear; thus, further studies are needed.

14.
Jpn J Clin Oncol ; 49(9): 823-831, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162583

RESUMO

BACKGROUND: Recent findings have shown that inflammation indices are associated with prognosis in various malignancies. However, the usefulness of inflammation indices including platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and prognostic nutritional index for gastrointestinal stromal tumors (GISTs) remains controversial. METHODS: We retrospectively reviewed 340 primary localized GIST patients who had received surgical resection between 2005 and 2015 to investigate the effect of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and prognostic nutritional index on prognosis. 206 patients were selected by propensity score matching to control selection biases. RESULTS: Kaplan-Meier analysis and the log rank test demonstrated that high prognostic nutritional index (≥43.9) was significantly correlated with better recurrence-free survival (RFS) (P<0.001). Among the three inflammatory indices, only preoperative high prognostic nutritional index was an independent prognostic factor for survival [hazard ratio (HR) 0.509; 95% confidence interval (CI) 0.266-0.872; P = 0.031] in multivariate analysis. After propensity score matching, elevated prognostic nutritional index was still a predictor for RFS (HR = 0.498; 95% CI 0.253-0.971; P = 0.042) in the multivariate analyses. In addition, prognostic nutritional index was a significant prognostic factor for GISTs within the National Institutes of Health (NIH) high and very low/low-risk categories. Incorporation prognostic nutritional index into the NIH risk criteria improved the prognostic stratification (c-index, 0.725 vs. 0.686, p = 0.039). CONCLUSIONS: High prognostic nutritional index is a predictor of improved survival for surgically resected GISTs and incorporation prognostic nutritional index into NIH risk criteria improves the predictive accuracy.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Avaliação Nutricional , Pontuação de Propensão , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Feminino , Humanos , Inflamação , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Adulto Jovem
15.
Cancer Manag Res ; 11: 4917-4930, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213910

RESUMO

Aim: Identifying high-efficiency prognostic markers for colorectal cancer (CRC) is necessary for clinical practice. Increasing evidence demonstrates that apolipoprotein C1 (APOC1) promotes carcinogenesis in some human cancers. However, the expression status and biological function of APOC1 in CRC remain unclear. Materials and methods: We detected the association between APOC1 expression and clinicopathological features in 140 CRC patients by immunohistochemistry. Small interfering RNA (siRNA) technology was used to downregulate APOC1 expression in CRC cells. Cell proliferation was estimated by CCK8 and clonogenic assays. The cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were examined by a transwell assay. Gene set enrichment analysis (GSEA) and protein expression of signaling pathways were used to suggest the possible APOC1-associated pathways in CRC. Results: APOC1 was highly expressed in CRC tissues. High immunohistochemistry (IHC) expression of APOC1 was correlated with the N stage, M stage and TNM stage. High IHC APOC1 expression in CRC tissues was associated with poor prognosis. Univariate and multivariate Cox regression analyses showed that APOC1 was an independent risk factor for OS. Cell proliferation of CRC cell lines was inhibited by the downregulation of APOC1. Moreover, si-APOC1 transfection induced cell cycle arrest but low apoptosis increases by regulating the expression of related proteins. Cell migration and invasion were also inhibited by the downregulation of APOC1. The Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA COAD-READ) dataset analyzed by GSEA showed that APOC1 might be involved in the mitogen-activated protein kinase (MAPK) signaling pathway, which was further preliminarily confirmed by Western blotting. Conclusion: APOC1 was overexpressed in CRC tissues, and a high level of APOC1 contributed to a poor prognosis. APOC1 expression influenced the cell proliferation ability and motility capacity of CRC via the MAPK pathway. APOC1 could act as a novel prognostic biomarker in CRC.

16.
Protein Pept Lett ; 26(10): 776-784, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31208304

RESUMO

BACKGROUND: Porcine circovirus and Mycoplasma hyopneumoniae can cause respiratory diseases in pigs, which cause serious economic loss in the worldwide pig industry. Currently, these infections are mainly prevented and controlled by vaccination. The new vaccines on the market are mainly composed of subunits and inactivated vaccines but usually have lower antigenicity than traditional live vaccines. Thus, there is an increasing need to develop new adjuvants that can cause rapid and long-lasting immunity to enhance the antigenic efficacy for vaccines. Studies have shown that meningococcal porin PorB can act as a ligand to combine with Toll-like receptors to activate the production of immunological projections and act as a vaccine immunological adjuvant. OBJECTIVE: In this article, we expressed and purified the recombinant PorB protein and verified its immunogenicity against porcine circovirus type 2 and Mycoplasma hyopneumoniae genetically engineered vaccine. METHODS: In this article, we used prokaryotic expression to express and purify recombinant PorB protein, four different concentrations of PorB protein, Freund's adjuvant with two genetically engineered vaccines were combined with subcutaneous immunization of mice. RESULTS: Our study shows that the appropriate dose of the recombinant protein PorB can enhance the levels of humoral and cellular responses induced by two genetically engineered vaccines in a short period of time in mice. The PorB adjuvant group may cause statistically higher antibody titers for both genetically engineered vaccines compared to Freund's commercial adjuvant (P<0.001). CONCLUSION: The recombinant protein PorB may be a good candidate adjuvant for improving the protective effect of vaccines against porcine circovirus type 2 and Mycoplasma hyopneumoniae, and the protein can be used for future practical applications.


Assuntos
Adjuvantes Imunológicos/farmacologia , Circovirus/metabolismo , Mycoplasma hyopneumoniae/metabolismo , Porinas/metabolismo , Vacinação/métodos , Vacinas Virais/farmacologia , Animais , Linhagem Celular , Proliferação de Células , Feminino , Linfócitos/citologia , Meningite/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Porinas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Solubilidade , Suínos , Receptores Toll-Like/metabolismo
17.
Diagn Pathol ; 14(1): 60, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31221177

RESUMO

BACKGROUND: MRE11, a protein known to play a vital role in DNA double-strand break repair, is associated with the prognosis of a variety of tumours, but there are few studies regarding the role of MRE11 in gastric carcinoma (GC). The present study aimed to explore the clinicopathological significance and prognostic value of MRE11 expression in GC. METHODS: Data from the TCGA, GEO and Oncomine databases were analysed to assess MRE11 mRNA levels in GC. The prognostic role of the level of MRE11 mRNA was examined via the Kaplan-Meier plotter. MRE11 protein expression in tumour tissues from 155 GC patients was analysed by immunohistochemistry. Relationships between MRE11 expression and clinicopathological characteristics, overall survival (OS) and recurrence-free survival (RFS) were evaluated by Cox proportional hazards regression models and Kaplan-Meier survival curves. RESULTS: The results of bioinformatics analysis showed that MRE11 mRNA levels in GC tissues were higher than those in normal tissues (P < 0.01). Tissue microarray analysis showed that MRE11 protein expression was increased in GC tissues (P < 0.001), and MRE11 overexpression in GC tissues was significantly related to lymph node metastasis (P < 0.05), distant metastasis (P < 0.05) and tumour-node-metastasis stage (P < 0.05). Kaplan-Meier analyses showed that patients with GC who exhibited MRE11 overexpression had worse OS and RFS. According to Cox proportional hazards analyses, MRE11 overexpression was an independent prognostic factor for OS and RFS in these GC patients. CONCLUSIONS: MRE11 overexpression is significantly associated with poor prognosis, and MRE11 may serve as a prognostic biomarker in GC patients.


Assuntos
Metástase Linfática/patologia , Proteína Homóloga a MRE11/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica/métodos , Metástase Linfática/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/metabolismo
18.
J Cancer ; 10(6): 1444-1452, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031854

RESUMO

Background: Specific guidelines recommend at least 15 or 16 lymph nodes (LNs) be examined to adequately assess nodal category of gastric cancer (GC), but the requirement for minimum number of regional LNs retrieval is not mentioned. This study aims to investigate survival significance from various numbers of perigastric (N1) LNs retrieval and to determine an optimal number harvested in such region. Study design: From April 1994 to March 2012, 1003 resectable GC patients with at least 15 LNs examined were included. Patients with at least 15 N1 nodes retrieval were assigned into study group, with the rest into control group. The 5-year overall survival (OS) rate was compared between two groups, and an optimal number of examined N1 nodes was detected by a survival joinpoint analysis. Results: 635 (63.3%) patients in study group had median 22 (range, 15-75) N1 nodes and 3 (range, 0-74) positive N1 nodes retrieval, with median 10 (range, 0-14) N1 nodes and 1 (range, 0-29) metastatic N1 nodes examined in control group. The number of N1 nodes retrieval was associated with tumor location (P=0.007), tumor stage (P<0.001) and total number of harvested LNs ( r =0.691, P<0.001). Median survival time (79.0 vs. 72.0 months, P=0.462) and actual 5-year OS rate (41.0% vs. 39.2%, P=0.463) were slightly improved in study group compared with control group, with significance obtained via stage-by-stage analysis. The joinpoint analysis indicated that at least seven N1 nodes retrieval achieved survival significance (81.0 vs. 35.0 months, P=0.036), with survival superiority remained until reaching up to 15 N1 nodes. Conclusion: Adequate retrieval of perigastric LNs is essential for radical gastrectomy. A harvest of at least 7-15 perigastric LNs could achieve long-term survival benefit for GC patients.

19.
Mol Med Rep ; 19(5): 3955, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30896791

RESUMO

The authors wish to retract their article entitled "Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts" published in Molecular Medicine Reports 15, 3690­3698, 2017. Following the publication of this article, the authors noted that the description of the reprogramming method and cell cultured conditions in the article was inconsistent with the experimental facts, due to their oversight and personnel issues in terms of who performed the experimental work and who wrote up the paper. Some of the experimental approaches were wrongly described in the Materials and methods section. Namely, the feeder cells which were used in this reprogramming were mouse embryonic fibroblasts, not guinea fibroblast cells, as was reported; the reprogramming medium contained 15% knockout serum replacement; the culture medium contained 10% ESC qualified fetal bovine serum and 10% knockout serum replacement; and 293T cells were transfected using the Quick Shuttle­293 system. Due to the authors' oversight, Figs 2A and C, and Fig. 3 on p. 3,694 do not match with the textual description. In view of these serious errors, which the authors are not able to rectify, they have requested that this article be retracted from the publication. All the named authors agree to this retraction. The authors regret any inconvenience to the readers that this retraction will cause.

20.
Oncogenesis ; 8(3): 13, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783098

RESUMO

Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial-mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations. Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, we show that the E3-ubiquitin ligase FBXW7 directly binds and degrades the EMT-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. Loss of FBXW7 induces an EMT that can be effectively reversed by knockdown of ZEB2. The FBXW7-ZEB2 axis regulates such important cancer cell features, as stemness/dedifferentiation, chemoresistance and cell migration in vitro, ex vivo and in animal models of metastasis. High expression of ZEB2 in cancer tissues defines the reduced ZEB2 expression in the cancer-associated stroma in patients and in murine intestinal organoids, demonstrating a tumour-stromal crosstalk that modulates a niche and EMT activation. Our study thus uncovers a new molecular mechanism, by which the CRC cells display differences in resistance to chemotherapy and metastatic potential.

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